Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes

Abstract

The antigenic polymorphism of HIV-1 is a major obstacle in developing an effective vaccine. Accordingly, we screened random peptide libraries (RPLs) displayed on phage with antibodies from HIV-infected individuals and identified an array of HIV-specific epitopes that behave as antigenic mimics of conformational epitopes of gp120 and gp41 proteins. We report that the selected epitopes are shared by a collection of HIV-1 isolates of clades A–F. The phage-borne epitopes are immunogenic in rhesus macaques, where they elicit envelope-specific antibody responses. Upon intravenous challenge with 60 MID50 of pathogenic SHIV-89.6PD, all monkeys became infected; however, in contrast to the naive and mock-immunized monkeys, four of five mimotope-immunized monkeys experienced lower levels of peak viremia, followed by viral set points of undetectable or transient levels of viremia and a mild decline of CD4+ T cells, and were protected from progression to AIDS-like illness. These results provide a new approach to the design of broadly protective HIV-1 vaccines.

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Figure 1: Vaccine schedule and prechallenge antibody responses.
Figure 2: Post-challenge levels of viremia and CD4+ T lymphocytes. Immunization and challenge schedule was as in Fig. 1a.
Figure 3: Post-challenge antibody response.

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Acknowledgements

We thank R. Byrum for assisting with animal procedures; V. Hirsh and C. Brown for in situ hybridization; J. Hadelsberger for FACS analysis; B. Mathieson, M.A. Martin, C. Lane and J.R. Mascola for critical reading of the manuscript; Yichen Lu for supplying the SHIV-89.6PD seed stock; and P. Earl for the gift of go140-89.6. This work was supported in part by grants from AIRC, ISS. Telethon and MURST.

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Correspondence to Giuseppe Scala.

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